Cilloni Daniela, Petiti Jessica, Campia Valentina, Podestà Marina, Squillario Margherita, Montserrat Nuria, Bertaina Alice, Sabatini Federica, Carturan Sonia, Berger Massimo, Saglio Francesco, Bandini Giuseppe, Bonifazi Francesca, Fagioli Franca, Moretta Lorenzo, Saglio Giuseppe, Verri Alessandro, Barla Annalisa, Locatelli Franco, Frassoni Francesco
Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy.
Department of Pediatric Hemato-Oncology and Stem Cell and Cellular Therapy Laboratory, Institute G. Gaslini, Largo G Gaslini, 16147 Genova, Italy.
J Clin Med. 2020 Jun 1;9(6):1670. doi: 10.3390/jcm9061670.
During the phase of proliferation needed for hematopoietic reconstitution following transplantation, hematopoietic stem/progenitor cells (HSPC) must express genes involved in stem cell self-renewal. We investigated the expression of genes relevant for self-renewal and expansion of HSPC (operationally defined as CD34+ cells) in steady state and after transplantation. Specifically, we evaluated the expression of ninety-one genes that were analyzed by real-time PCR in CD34+ cells isolated from (i) 12 samples from umbilical cord blood (UCB); (ii) 15 samples from bone marrow healthy donors; (iii) 13 samples from bone marrow after umbilical cord blood transplant (UCBT); and (iv) 29 samples from patients after transplantation with adult hematopoietic cells. The results show that transplanted CD34+ cells from adult cells acquire an asset very different from transplanted CD34+ cells from cord blood. Multivariate machine learning analysis (MMLA) showed that four specific gene signatures can be obtained by comparing the four types of CD34+ cells. In several, but not all cases, transplanted HSPC from UCB overexpress reprogramming genes. However, these remarkable changes do not alter the commitment to hematopoietic lineage. Overall, these results reveal undisclosed aspects of transplantation biology.
在移植后造血重建所需的增殖阶段，造血干/祖细胞（HSPC）必须表达参与干细胞自我更新的基因。我们研究了与HSPC（定义为CD34+细胞）自我更新和扩增相关的基因在稳态及移植后的表达情况。具体而言，我们评估了91个基因的表达，这些基因通过实时PCR在从以下样本中分离出的CD34+细胞中进行分析：（i）12份脐带血（UCB）样本；（ii）15份骨髓健康供体样本；（iii）13份脐带血移植（UCBT）后的骨髓样本；以及（iv）29份成人造血细胞移植后患者的样本。结果显示，来自成人细胞的移植CD34+细胞获得了与来自脐带血的移植CD34+细胞非常不同的特征。多变量机器学习分析（MMLA）表明，通过比较四种类型的CD34+细胞可以获得四种特定的基因特征。在一些但并非所有情况下，来自脐带血的移植HSPC过表达重编程基因。然而，这些显著变化并未改变对造血谱系的定向分化。总体而言，这些结果揭示了移植生物学中未被揭示的方面。
